This document discusses various experimental models used to test potential anti-arthritic agents, including adjuvant arthritis in rats, terpentine oil-induced edema, and formaldehyde-induced arthritis. Adjuvant arthritis is induced in rats by injecting complete Freund's adjuvant or synthetic adjuvants and results in hind paw swelling that can be monitored over time. Terpentine oil injected into rat knee joints causes acute, non-immunological edema assessed by measuring joint diameter changes. Formaldehyde injections into rat paws induce chronic, non-immunological arthritis evaluated by paw diameter increases over 10 days. These preclinical models are used to screen anti-arthritic drugs.

1. ANTI-ARTHRITIS AGENT
Presented By –
SMITA CHOUDHARY
M.Pharm II Semester

2. ANTIARTHRITIC AGENTS
Rheumatoid arthritis (RA) is a chronic disabling disease
affecting around 1% of the population.
Much progress has been made in recent years towards
the identification of mediators that contribute to the
pathogenesis of RA,and a numbers of studies have
pointed to a pivotal role for tumour necrosis factor-
apha(TNFa)in the disease process.Indeed,the success
of biological inhibitors of TNFa (Elliott et al.1993,1994
a,b;Moreland et al.1997;Weinblatt et al.1999) in the
clinic is a testament to the pathological significance of
this cytokine in RA.

3. 1-ADJUVANT ARTHRITIS
Adjuvant Arthritis Rat adjuvant arthritis is an experimental model
of polyarthritis which has been widely used for preclinical
testing of numerous anti-arthritic agents which are either under
preclinical or clinical investigation or are currently used as
therapeutics in this disease.
Male Lewis rats (165-200 grams, 7/group) are generally used in
studies of adjuvant arthritis. The disease develops in females
but is much more variable in onset and severity. Animals
should be allowed to acclimate for at least 3 days prior to
initiation of experimentation.

4. Induction of adjuvant disease can be done with either Freunds
complete (FCA) supplemented with mycobacterium or by
injection of the synthetic adjuvant N, Ndioctylddecyl-N', N-
bis(2-hydroxy-ethyl) propanediamine (LA)7. Adjuvant can be
injected at the base of the tail or in one of the foot pads. If
injection is into the footpad, it allows study of the acute
inflammatory reaction in that local area as well as the
immunological reaction that develops approximately 9 days
later in the contralateral paw and various organs.
Hind paw swelling is monitored from day 9 (onset of disease)
to15 or greater depending on duration desired.

5. In the later stages of disease (day 12+), adjuvant arthritis rats
are often relatively immobile due to severity of paw swelling
and so require special care to insure that they have access to
water and food.
Treatments are initiated on day 0 (prophylactic model dosing)
or day 8 (therapeutic model).
Various stress-related factors including manipulations during
the test period (pharmacokinetic sampling), frequency of
dosing (QD vs BID) or type of vehicle used can influence the
disease progression.

6. The newer biologic agents such as the interleukin-1 receptor
antagonist (IL-1ra) and soluble TNF receptors also have
activity in this model9-12. Demonstration of efficacy with IL-
1ra is dependent on maintaining sufficient blood levels for
prolonged receptor antagonism either by continuous infusion
methodologies or by the use of slow release vehicles.

7. 2.TERPENTINE OIL INDUCED EDEMA
Terpentine induced a acute and non-
immunological disease edema joint,preferably
Albino rat used 0.2ml injected into the sinovial
cavity the animal.
In the right knee of animal after 30mins of the
test drug administration.
The diameter of joint is measured at an internal
of one hours upto 6hrs by using micro meter
screb gauge.

8. Terpentine oil induced joint edema character to
increase the vascularity per aldehyde and marked
vasodilation through the sequencial release of
cytokines his,serotonin in early phase followed by
kinin like (bradykinin) substance in the termident
phase and PG in late phase.
Inhibition of terpentine induced joint edema reflex
overall anti-inflammatory of effect of the test
drug.

9. PARAMETERS TO BE EQVALUATED-
1-% changed in joint diameter
2-X-Ray photography of joint
3-Histopathology of joints

10. 3.FORMALDEHYDE INDUCED
ARTHRITIS
Formaldehyde induced chronic non-immunological
arthritis.HCHO is injected as a substance injection of
0.1ml of HCHO solution (20%).
Similar dose of HCHO is repeated on drug three time.
The test drug is adminiseredon day one 30min before
the 30min administration of HCHO.The
administration of test drug may continue up to 10-45
days.

11. Arthritis is assested to measuring the increase the
paw diameter over a period of 10 days using
micrometer screw gauze.
It is one of the most suitable method to evaluation
antiproferative activity and screened antiarthritis
agents.
HCHO induced by bi-phasic response presence
early neurogenic compound and followed by a
later tissue mediated response.Overall HCHO
induced a proliferative global edema.

12. PARAMETER TO BE EQUAL EVALUATED-
1-% Change in paw diameter
2-X-ray
3-Histopathology of joints